A key goal of this collaboration will include the further development of small molecule biased ghrelin receptor ligand(s), and its validation in biochemical and behavioral assays as a potential pre-clinical and clinical candidate for the treatment of eating disorders or chemical drug addiction. During this period, the project team conducted high-throughput screening against a number of NCGC's chemical libraries using a cell-based GHSR1a B-arrestin activation assay. This primary HTS campaign was followed by additional confirmation, a number of novel scaffolds were identified. Initial hits compounds were analyzed by calcium signaling and B-arrestin translocation secondary assays for their ability to activate G protein or B-arrestin intracellular signaling pathways, respectively. Candidate lead scaffolds were selected for further evaluation and optimization based on promising activity profiles. To continue optimization of lead compounds, the collaborating laboratories have formed an interdisciplinary team with extensive expertise in drug discovery, biochemical and behavioral assays of GPCRs, and testing of drugs in animal models of addictive behaviors in wild type and genetically modified mice.